Structural And Functional Studies On RNA Nuclear Retention Mediated By Paraspeckles: A Novel Gene Regulation
Funder
National Health and Medical Research Council
Funding Amount
$290,978.00
Summary
Dynamic interactions between proteins and nucleic acids are essential process in gene regulation, where aberrant regulation leads to various diseases including cancers. The project aims to examine the interactions between paraspeckle proteins and nucleic acid molecules via determination of the structures of protein-nucleic acid complexes at the atomic level. The results will provide a better understanding of a recently discovered gene regulation mechanism and a basis for new gene therapy.
Transport And Egress Of Herpes Simplex Virus In Neurones
Funder
National Health and Medical Research Council
Funding Amount
$592,023.00
Summary
Herpes simplex virus (HSV) enters the human body via the skin before entering the termini of nerve cell processes. It is transported along these processes to the body of the nerve cell. HSV lies dormant within these nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported back down the nerve cell processes to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this grant is to determine how HSV is transpor ....Herpes simplex virus (HSV) enters the human body via the skin before entering the termini of nerve cell processes. It is transported along these processes to the body of the nerve cell. HSV lies dormant within these nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported back down the nerve cell processes to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this grant is to determine how HSV is transported within nerve cells at the molecular level. Recent discoveries have shown how virus transport in nerve cells is dependent on interactions between specific viral proteins and cellular motor proteins and how the virus escapes from nerves to infect skin and cause disease. Such information on viral transport will allow development of inhibitors of this process which may be candidates for use as antivirals for control of recurrent herpes simplex. In addition, this information will allow the virus to be exploited for use in gene therapy to introduce DNA into human nerve cells to correct genetic abnormalities. Finally this data will assist in understanding similar mechanisms for other viruses transported in nerve cells such as those causing shingles and rabies.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100089
Funder
Australian Research Council
Funding Amount
$700,000.00
Summary
Super-resolution fluorescence microscopy. The prestigious journal Nature Methods named super-resolution fluorescent microscopy as the Method of the Year 2008. This recognition is justified because fluorescent imaging on the molecular scale will revolutionise biological sciences. It will literally change the way we see the smallest building blocks of life and this allows researchers to identify the function of proteins and lipids in health and disease. This breakthrough technology is currently no ....Super-resolution fluorescence microscopy. The prestigious journal Nature Methods named super-resolution fluorescent microscopy as the Method of the Year 2008. This recognition is justified because fluorescent imaging on the molecular scale will revolutionise biological sciences. It will literally change the way we see the smallest building blocks of life and this allows researchers to identify the function of proteins and lipids in health and disease. This breakthrough technology is currently not available to researchers in Australia. Super-resolution fluorescence microscopy would extend Australia's leading position in the fundamental biological sciences, bio- and nano-technologies as well as imaging and microscopy.Read moreRead less
Transport, Assembly And Egress Of Herpes Simplex Virus In Neurones
Funder
National Health and Medical Research Council
Funding Amount
$639,661.00
Summary
Herpes simplex viruses 1 and 2 are important pathogens, causing encephalitis, blindness and severe neonatal infection but they also enhance the acquisition of HIV three-fold. The transport of the virus to and from the periphery to the spinal cord is a key component of their life cycle. Determination of the exact mechanism will assist in a general understanding of nerve function and the development of new strategies for antiviral drugs.
Investigation of a Phagocytic Synapse in the Uptake of Apoptotic Cells. Rapid clearance of cells that die by apoptosis is crucial for embryonic development, tissue turnover, and after inflammatory events. Specialised phagocytes engulf the apoptotic cell corpses in a way that minimises inflammation and prevents autoimmunity. Genetic studies have identified the key evolutionary receptors involved, but the molecular basis of this phagocytosis is still poorly understood. We have developed, and seek ....Investigation of a Phagocytic Synapse in the Uptake of Apoptotic Cells. Rapid clearance of cells that die by apoptosis is crucial for embryonic development, tissue turnover, and after inflammatory events. Specialised phagocytes engulf the apoptotic cell corpses in a way that minimises inflammation and prevents autoimmunity. Genetic studies have identified the key evolutionary receptors involved, but the molecular basis of this phagocytosis is still poorly understood. We have developed, and seek to establish, an integrated model that incorporates new findings to explain how the distinctive functions of specialised receptors can be orchestrated to achieve this function. A successful outcome to the project will provide new knowledge of value to human health.Read moreRead less
Regulation of MHC-I and ICAM-1 by flavivirus, West Nile. This project investigates the intracellular signalling pathway responsible for the expression of genes which are critical to our immune response. We have demonstrated in a mouse model that high levels of expression of two of these genes in flavivirus encephalitis are associated with a survival advantage. We would expect this project to provide basic new information about the mechanisms of expression of these genes as well as information ab ....Regulation of MHC-I and ICAM-1 by flavivirus, West Nile. This project investigates the intracellular signalling pathway responsible for the expression of genes which are critical to our immune response. We have demonstrated in a mouse model that high levels of expression of two of these genes in flavivirus encephalitis are associated with a survival advantage. We would expect this project to provide basic new information about the mechanisms of expression of these genes as well as information about the interaction of this family of viruses, flavivirus with the host.Read moreRead less
Lipid raft and cyotoskeleton organization: How membrane domains give cells direction. For a large number of cells in our body it is imperative that they are able to orientate themselves relative to their environment, sense direction and translate incoming signals. To do so it is hypothesised that lipids on the cell surface are redistributed to form specialized domains. An asymmetric distribution of membrane domains can provide cells with a front and rear end and can further concentrate and co-or ....Lipid raft and cyotoskeleton organization: How membrane domains give cells direction. For a large number of cells in our body it is imperative that they are able to orientate themselves relative to their environment, sense direction and translate incoming signals. To do so it is hypothesised that lipids on the cell surface are redistributed to form specialized domains. An asymmetric distribution of membrane domains can provide cells with a front and rear end and can further concentrate and co-ordinate signalling molecules to a specific site. The project will determine the role of lipid domain in stabilizing cell shape and their remodelling during cell migration, the digestion of foreign particles and the formation of cell-cell contacts.Read moreRead less
Characterisation of p14ARF intracellular trafficking pathways. Over 3500 new cases of melanoma are diagnosed in NSW each year, and one of the most important proteins involved in suppressing melanoma initiation or growth is p14ARF. This project will characterise the movement and functions of this protein with the aim of identifying novel targets for more effective drug therapies.
Discovery And Mechanisms Of Host Cell Factors In HIV Uncoating
Funder
National Health and Medical Research Council
Funding Amount
$635,098.00
Summary
HIV entry into the host cell involves release of its capsid, a protein shell protecting the viral genome. The capsid hijacks host proteins to cloak itself from cellular defenses while the cell has evolved sensors that can block viral infection. This proposal aims to discover proteins involved in this arms race between host and virus and decipher how they control capsid disassembly. This insight will help design new drugs against HIV infection and new ways to deliver genes for gene therapies.